Klebsiella pneumoniae bloodstream infections in hospitalised children at Red Cross War Memorial Children's Hospital : 2006 - 2011

Background: Klebsiella pneumoniae (KP) is a significant paediatric bloodstream pathogen in children. There is little data about KP in South African children. The focus for the present study was to address this knowledge gap. Methods: This study addressed a retrospective case notes review on bloodstream Klebsiella pneumoniae infections at a children's hospital in Cape Town, South Africa 2006-2011 using conventional descriptive and comparative statistical methods. Results: Of 410 hospitalised children with laboratory confirmed KP bloodstream infection (KPBSI), 339 (83%) were presumed extended-spectrum β-lactamase (ESBL) producing isolates. The median age (interquartile range, IQR) was 5.0 (2-16) months, 212 (51.7%) were male, 82 (20%) were HIV-infected, and 241 (58.8%) were moderately or severely underweight. The infection was nosocomial or healthcare-associated in 389 (95%) children and community-acquired in 21 (5%) children. Significant risk factors for the acquisition of ESBL-KP bloodstream infection included cephalosporin exposure in the preceding 12 months prior to the KPBSI p=<0.0001: aRR 1.25 (95% CI: 1.15-1.36); and those who had intravenous infusions for more than 3 days prior to the KPBSI, p=0.004: aRR 1.18 (95% CI: 1.05-1.31)

Klebsiella pneumoniae bloodstream infections at a South African children’s hospital 2006–2011, a cross-sectional study

Background: Klebsiella pneumoniae (KP) is a significant paediatric bloodstream pathogen in children. There is little data from Africa. In this study we describe the epidemiology of multi-drug resistant Klebsiella pneumoniae bloodstream infection (KPBSI) at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Methods: We conducted a retrospective cross-sectional study of KPBSI from 1 January 2006 to 31 December 2011 using conventional descriptive and inferential statistical methods. Results: Of 410 hospitalised children with laboratory confirmed KPBSI, 339 (83 %) were caused by extendedspectrum β-lactamase (ESBL) producing isolates. The median age (IQR) was 5.0 (2–16) months, 212 (51.7 %) were male, 82 (20 %) were HIV-infected, and 241 (58.8 %) were moderately or severely underweight. The infection was hospital-acquired or healthcare-associated in 389 (95 %) children and community-acquired in 21 (5 %) children. Significant risk factors for ESBL-KPBSI included cephalosporin exposure in the 12 months prior to the KPBSI, adjusted risk ratio (aRR) 1.18 (95 % CI: 1.06–1.31); HIV infection, aRR 1.14 (1.04–1.25), and intravenous infusions for more than 3 days before the KPBSI, aRR 1.15 (95 % CI: 1.04–1.28). A total of 109 (26.6 %) children died within 30 days of the KPBSI, their median age was four (IQR 1–11) months. The median (IQR) time between KPBSI and death was three (1–9) days. HIV-infection, aRR 2.44(95 % CI: 1.59–3.74); skin erosions at the time of KPBSI, aRR 2.15 (95 % CI: 1.54–3.00); being in PICU at the time of the KPBSI, aRR 1.64 (95 % CI: 1.03–2.61) or needing PICU admission after developing KPBSI, aRR 1.72 (95 % CI: 1.10–2.70) were significant risk factors for death. Conclusion: ESBL-producing KP is an important cause of laboratory confirmed bloodstream infection in hospitalised children and is associated with high mortality

Initial experience of a public sector antiretroviral treatment programme for HIV-infected children and their infected parents

Objective. To describe the initial experience of treating HIVinfected children and their infected parents with antiretroviral therapy. Design. Prospective, cohort study. Setting. Tertiary, referral hospital. Patients. HIV-infected children and their parents. Methods. This report focuses on the early response of children to highly active antiretroviral therapy (HAART). Children were followed up at 4-weekly intervals. Monitoring included initial and yearly viral load measurements, baseline and 6- monthly CD4 counts and 4-weekly adherence checks. Results. Between August 2002 and June 2003, 80 children were enrolled in the programme, representing a follow-up period of 23.9 patient-years. Seventy-five children had severe clinical disease, severe immune suppression, or a combination of the two. The response of children who had received HAART for ≥ 6 months (N = 17) was assessed. There was no change in mass z-score (p = 0.11) or length z-score (p = 0.37), but a significant increase in CD4 percentage (p < 0.0001) during the first 6 months of therapy. Six-month viral loads were available for 12 children. There was a significant drop in viral load (p = 0.001) and 9 achieved undetectable levels by 6 months. Most children achieved ≥ 85% adherence. By June 2002, 67 children (84%) were relatively well, 1 had B-cell lymphoma, 7 (8.8%) had died, 4 (5%) were lost to follow-up and 1 was withdrawn from the programme. Of 57 children who completed 3 months of HAART, 12 were admitted a total of 17 times for infectious complications. There were no severe drug reactions. Three of 7 mothers on HAART received treatment through the programme. Conclusion. These initial results suggest that many HIVinfected children in the public sector will benefit from antiretroviral therapy. However, both ambulatory and inpatient facilities are required to manage children on HAART comprehensivel

The prevalence of liquid chromatography-tandem mass spectrometry confirmed paediatric poisoning at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa

Background Paediatric poisoning is a common presentation to emergency departments worldwide. There is a paucity of data on the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS), in the management of paediatric poisoning in low-and middle-income countries (LMICs). In high-income countries, most studies are retrospective, and few include children. Objective The study describes the prevalence of liquid chromatography-tandem mass spectrometry confirmed paediatric poisoning at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Methods Children admitted with suspected poisoning between 1 January 2017 and 31 December 2017, were recruited. All patients had a urine and/or blood sample sent for LC-MS/MS toxicology. Data collected included demographic data, clinical features, investigations, management, outcome and social interventions. Results One hundred fifty-two children, with median age of 39 (IQR 25–61) months were enrolled of which 128 (84%) were poisoning cases. Of the 128 poisoning cases, 88 (69%) presented with a history of ingesting a known substance, 16 (12%) an unknown substance and 24 (19%) were cases of occult poisoning. LC-MS/MS was able to identify a substance in 92% of the cases of occult poisoning. In those who had presented with a seemingly known substance, LC-MS/MS found a different substance in 15 cases. LC-MS/MS was also able to detect multiple drugs in 40 patients. Of the poisoning cases, six (5%) cases were attempted homicide cases and 5 (4%) cases were attempted suicide cases. No children died. Individualized social interventions were instituted in poisoning cases. Emergency placement safety reasons was required in 6 children. Conclusion When the limitations are known, LC-MS/MS is useful in identifying cases of occult poisoning, identifying patients who have ingested multiple substances and/or an unknown substance and when targeted towards child protection. As LC-MS/MS is an expensive test, it should be used judiciously in LMICs

Antiretroviral treatment for children

No Abstract. South African Medical Journal Vol. 96(9) (Part 2) 2006: 988-99

Antiretroviral treatment for children

Objective: To describe the response of children during their first year on highly active antiretroviral therapy (HAART). Design: Retrospective, descriptive. Setting. Tertiary, referral hospital. Subjects: All HIV-infected children commenced on HAART from 1 August 2002 until 31 December 2004. Outcome measures: Children were retrospectively restaged using the WHO 4-stage clinical classification and CDC immunological staging system. After commencing HAART, patients were assessed at monthly intervals for the first 6 months and thereafter mostly 3-monthly. Baseline and 6- monthly CD4 counts and viral loads were performed. Results. Of 409 children commenced on HAART, 50.6% were < 2 years old, 62.7% had severe clinical disease and 76.6% had severe immune suppression. After 1 year, 65.8% were alive and continued HAART at the hospital, 11.2% had been transferred to another antiretroviral site, 15.4% had died, 4.6% were lost to follow-up and treatment had been discontinued in 2.9%. Kaplan-Meier survival estimate for 407 children at 1 year was 84% (95% confidence interval (CI) 80 - 87%). On multivariate analysis, survival was adversely affected in children with WHO stage 4 v. stage 2 and 3 disease (adjusted hazard ratio (HR): 5.26 (95% CI 2.25 - 12.32), p = 0.000), age < 12 months (adjusted HR: 2.46 (95% CI 1.48 - 4.09), p = 0.001) and CD4 absolute count (per 100 cell increase) (adjusted HR: 0.93 (95% CI 0.88 - 0.98), p = 0.013). In a separate multivariate model including only children with an initial viral load (N = 367), viral load r 1 million copies/ml (adjusted HR: 1.84 (95% CI 1.03 - 3.29)) and taking a protease inhibitor (PI)-based regimen (adjusted HR: 2.25 (95% CI 1.10 - 4.61)) were additionally independently associated with poorer survival; however, young age was not a significant predictor of mortality, after adjusting for viral load (p = 0.119). After 1 year of HAART 184/264 (69.7%) of children had a viral load < 400 copies/ml. Comparative analysis showed significant improvements in growth, immunological status and virological control. Conclusion: HAART can improve the health of many HIVinfected children with advanced disease, including those aged less than 2 years in resource-limited settings

A Comparison of Parenteral Phenobarbital vs. Parenteral Phenytoin as Second-Line Management for Pediatric Convulsive Status Epilepticus in a Resource-Limited Setting

Introduction: Pediatric convulsive status epilepticus (CSE) which is refractory to first-line benzodiazepines is a significant clinical challenge, especially within resource-limited countries. Parenteral phenobarbital is widely used in Africa as second-line agent for pediatric CSE, however evidence to support its use is limited.Purpose: This study aimed to compare the use of parenteral phenobarbital against parenteral phenytoin as a second-line agent in the management of pediatric CSE.Methodology: An open-labeled single-center randomized parallel clinical trial was undertaken which included all children (between ages of 1 month and 15 years) who presented with CSE. Children were allocated to receive either parenteral phenobarbital or parenteral phenytoin if they did not respond to first-line benzodiazepines. An intention-to-treat analysis was performed with the investigators blinded to the treatment arms. The primary outcome measure was the success of terminating CSE. Secondary outcomes included the need for admission to the pediatric intensive care unit (PICU) and breakthrough seizures during the admission. In addition, local epidemiological data was collected on the burden of pediatric CSE.Results: Between 2015 and 2018, 193 episodes of CSE from 111 children were enrolled in the study of which 144 met the study requirements. Forty-two percent had a prior history of epilepsy mostly from structural brain pathology (53%). The most common presentation was generalized CSE (65%) caused by acute injuries or infections of the central nervous system (59%), with 19% of children having febrile status epilepticus. Thirty-five percent of children required second-line management. More patients who received parenteral phenobarbital were at a significantly reduced risk of failing second-line treatment compared to those who received parenteral phenytoin (RR = 0.3, p = 0.0003). Phenobarbital also terminated refractory CSE faster (p &lt; 0.0001). Furthermore, patients who received parenteral phenobarbital were less likely to need admission to the PICU. There was no difference between the two groups in the number of breakthrough seizures that occurred during admission.Conclusion: Overall this study supports anecdotal evidence that phenobarbital is a safe and effective second-line treatment for the management of pediatric CSE. These results advocate for parenteral phenobarbital to remain available to health care providers managing pediatric CSE in resource-limited settings.Attachments: CONSORT 2010 checklistTrial registration: NCT03650270Full trial protocol available:https://clinicaltrials.gov/ct2/show/NCT03650270?recrs=e&amp;type=Intr&amp;cond=Status+Epilepticus&amp;age=0&amp;rank=